Capmaxen 200 mg | 56 Tablets | Generic Capmatinib

Capmaxen 200 mg (Capmatinib) general approval has been granted for adult patients as detected by an FDA test with metastatic non-small cell lung cancer with a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping on 10 August 2022.

On May 6, 2020, the FDA initially granted approval based on the overall response rate and duration of response observed in the GEOMETRY mono-1 trial. The subsequent regular approval was supported by data from 63 additional patients and 22 more months of follow-up, which confirmed response durability and verified clinical benefit.

This approval information was cited on the Capmatinib Approval page of the FDA website. 

Composition

Each film-coated tablet contains Capmatinib Hydrochloride INN, which is equivalent to Capmatinib 200 mg.

Clinical Pharmacology

Mechanism of Action

Capmaxen 200 mg is a tyrosine kinase inhibitor that targets MET, including the mutant variant built with exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that decreases its negative regulation, leading to increased MET signaling. Capmatinib, targeting a mutant MET variant, reduced anti-tumor activity at clinically attainable levels and in xenograft murine models of MET exon 14 skipping or MET amplification driven by human lung tumors. Capmatinib anti-phosphorylated MET at and beyond the level of HGF, MET amplification, and at subsequent levels in MET-dependent cancer cells.

Absorption

When Capmaxen 400 mg is taken orally by patients with metastatic non-small cell lung cancer, the highest blood concentration is usually reached within 1 to 2 hours, and its absorption after administration is estimated to exceed 70%.

Distribution

Capmatinib plasma protein binding is 96%, independent of capmatinib concentration. The visible mean volume of distribution at steady-state is 164 L. The blood-to-plasma ratio was 1.5, but decreased at higher concentrations to 0.9.

Dosing Information Mentioned on the FDA website

The general recommended dosage of Capmaxen for adults is 400 mg taken by mouth twice a day, with or without food. Tablets should be swallowed whole with water and not broken or split. Its safety and effectiveness in children have not been established in any clinical trials.

The dose may differ from person to person; follow the prescription instructions properly mentioned by a licensed health care professional.

Missed Dose

Take the missed dose as soon as possible or skip the dose if it is close to the next dose. Do not take a combined dose to make up for the missed dose. Medical attention is required for a missed dose and an overdose.

Side Effects of the Medication

The below adverse reactions were seen in less than 10% of the patients who took Capmaxen 200 mg tablets in GEOMETRY mono-1.

•       Edema: edema (swelling of the body’s outer parts with fluid), peripheral, generalized edema, face edema, localized edema, genital edema, eyelid edema, peripheral swelling, scrotal edema, and penile edema.
•       Musculoskeletal pain: Musculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, myalgia, neck pain, non-cardiac chest pain, pain in the extremity, pain in the jaw, and spinal pain.
•       Fatigue: It includes regular fatigue and asthenia.
•       Pyrexia: It includes increased body temperature.
•       Weight decreased
•       Nausea
•       Vomiting
•       Constipation
•       Diarrhea
•       Dyspnea
•       Cough: Upper airway cough syndrome and productive cough
•       Pneumonia: It includes pneumonia aspiration, pneumonia influenzal, pneumonia bacterial, lower respiratory tract infection and lung abscess.
•       Decreased Appetite
•       Rash: Pimples like rash, rash maculo-papular, eczema, erythema multiforme, rash macular, dermatitis.
•       Dizziness: It includes dizziness, vertigo, and positional vertigo.

Warnings and Precautions

Interstitial Lung Disease (ILD)/Pneumonia

Fatal pneumonia can occur in patients who are going to be treated with Capmaxen 200 mg. Evidence of pneumonia was found in 4.8% patients treated with the medication. Monitoring is required for new or pulmonary symptoms indicative of pneumonia, including dyspnea, fever, and cough.

Hepatotoxicity

Monitor liver function test, including ALT, AST, and bilirubin, before the start of the medication and every two weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing who develop increased transaminases or bilirubin. With the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue in accordance with prescribing information.

Pancreatic Toxicity

Monitor digestive enzymes (Amylase and lipase) at baseline and regularly during treatment with Capamatinib. Based on the severity of the adverse drug reactio,n temporarily withhold, dose reduce, or discontinue permanently with the help of a healthcare professional.

Risk of photosensitivity

Based on the findings from animal studies, there is a potential risk of photosensitivity reaction with Capamatinib. In GEOMETRY mono-1, it was recommended that patients use precautionary measures against ultraviolet exposure, such as the use of sunscreen or protective clothing during treatment. It is advised to limit direct ultraviolet exposure during the treatment.

Embryo-Fetal Toxicity

Based on the findings from animal studies and the mechanism of action, Capamatinib can cause fetal harm when administered to a pregnant woman. Oral administration of Capamatinib to pregnant rats and rabbits during the period of organogenesis resulted in malformation at exposure less than the human exposure based on the area under the curve at the 400 mg twice daily clinical dose. Female reproductive potentials should use effective contraception during treatment with Capmaxen and for one week after the last dose. It is advised for both females and males with reproductive potential to use effective contraception during treatment with Capmaxen for one week after the last dose.

Uses in a specific population

Pregnancy

Based on findings from animal studies and its mechanism of action, it can cause fetal harm when it is administered to a pregnant woman. Currently, there are no clinical data on the use of Capmaxen in pregnant women. In animal studies, oral administration to rats and rabbits during organ development caused malformations at exposure levels lower than those seen in humans at the 400 mg twice-daily dose based on AUC.

Lactation

No information is available on whether Capmatinib 200 mg (Capmaxen) or its metabolites pass into human or animal breast milk, or on their potential impact on nursing infants or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Capmaxen and for 1 week after the last dose.

Female and Male Reproductive Potential

Based on animal data, Capmaxen 200 mg can cause malformation at doses less than human exposure based on AUC at the 400 mg twice daily clinical dose. Verify pregnancy status for females of reproductive potential before starting treatment with Capmatinib tablet. Advise females of reproductive potential to use effective contraception during treatment with the medication and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with the medication and for 1 week after the last dose. 

Pediatric Use

The safety and effectiveness of the pediatric use of Capmatinib tablets have not been established. 

Geriatric Use

In the GEOMETRY mono-1 study, 61% of the 373 participants were aged 65 or older, and 18% were 75 or older. The study found no significant differences in safety or effectiveness between these older patients and younger participants.

Renal Impairment

For patients with mild to moderate kidney impairment, no dose adjustment of Capmatinib is necessary. Its use has not been evaluated in individuals with severe renal impairment, so medical guidance should be sought before use in such cases.

Manufacturer and Supplier Information

Capmaxen 200 mg (Capmatinib) is manufactured by Everest Pharmaceutical LTD. You can access this medication through Onus Pharma.

 Disclaimer: Information above is not for use as an alternative to medical information.